- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Domingues-Silva, B., Azzalin, C. M.Mammalian telomeric DNA comprises long tracts of tandem TTAGGG repeats. The same repeats are also found at internal chromosomal regions called interstitial telomeric sequences (ITSs). Telomeres are transcribed into UUAGGG-containing transcripts, named TERRA, which serve multiple functions in maintaining telomere integrity. Complementary RNAs containing C-rich telomeric repeats, named ARIA, have also been identified in few yeast mutants and mammalian cells with dysfunctional telomeres. The molecular features and functions of ARIA remain understudied, mainly due to its low abundance and the […]
- by Mabry, K. N., Donahue, E. K. F., Orgel, A. D., Keuchel, B., Kushner, M. G., Burkewitz, K.The neuronal endoplasmic reticulum (ER) extends from the soma into axons and dendrites to coordinate protein trafficking, lipid metabolism, inter-organelle organization, and calcium homeostasis. Conserved genes involved in shaping the tubular ER are implicated in neurodevelopment and neurodegeneration, suggesting that ER structure and dynamics influence neuronal health and drive pathogenesis. However, the links between ER morphology and neuronal function and resilience remain incompletely understood. While models typically depict the neuronal ER as a fully continuous network, here we show that […]
- by Li, L., Pohl, L., Hutloff, A., Niethammer, B., Thurley, K.Cytokine-mediated communication is a central mechanism by which immune cells coordinate activation, differentiation and proliferation. While mechanistic reaction-diffusion models provide detailed descriptions of cytokine secretion and uptake at the cellular scale, their computational cost limits their applicability to large and densely packed cell populations. Previously employed approximations of cytokine diffusion fields rely on assumptions that neglect the influence of cellular geometry and volume exclusion. In this work, we study a macroscopic description of cytokine diffusion and reaction dynamics based on […]
- by Juarez-Contreras, I., Kim, H., Budin, I.A hallmark of eukaryotic membranes is the pairing of lineage-specific sterols with characteristic sphingolipid species. Mammalian cell membranes are enriched in both cholesterol and long-chain sphingolipids like sphingomyelin, whereas fungi synthesize ergosterol and very long-chain sphingolipids with sugar-containing head groups. It has been proposed that these two lipid classes co-evolved to support membrane structure and organization. Here we investigated how sterol structure and sphingolipid chain length together control membrane order and phase behavior. In the yeast Saccharomyces cerevisiae, loss of […]
- by Zhou, B. P., Chu, T. L. H., Gallant, A. K., Wang, S., Bhat, T. A., Ghorayeb, R., Gough, C., Garcia, R. E., Pujana, M. A., Lim, C. J., Maxwell, C. A.The metastatic process initiates with collective cell invasion into surrounding tissues and axillary nodes, and subsequent colonization at a distant site. Previously, we found collective invasion is augmented during the G2 cell cycle phase, facilitated through Aurora kinase A (AURKA)-mediated centrosome polarization in the leader cell. Here, we identify cell cycle-associated gene signatures as overrepresented in axilla and liver metastatic sites, with AURKA expression strongly correlated with breast cancer metastasis signatures, and pan-cancer patient survival. Then, we show GFP-AURKA expression […]
- by Matsche, J., Fauser, J., Bansal, T., Leschinsky, N., Coleman, C., Karginov, A. V.Optogenetics enables researchers to control protein localization, interactions, and activity using photosensitive domains. The key desired properties for optogenetic tools include broad applicability, tight light-regulated control with high dynamic range, and tunability. Previously, we described an engineered light-sensitive switch, LightR, composed of two VVD domains connected by a flexible linker, enabling light-dependent allosteric control of protein activity through site-specific insertion. Here, we introduce enhanced LightR variants with improved dynamic range and faster activation kinetics. Through targeted modifications to the VVD […]
- by Joerg, M., Walz, L., Lander, M., bessler, l., Nathal, s., Freude, K. K., Endres, K., Helm, M., Friedland, K.tRNA modifications are critical regulators of RNA stability, decoding fidelity, and cellular stress adaptation, yet their contribution to human neurodegenerative disease remains poorly understood. Beyond their established functions in translational control, emerging evidence shows that RNA modifications influence neurogenesis, neurodevelopment, neuronal function, brain-cell differentiation, and cellular plasticity. Consequently, dysregulation of these molecular processes is increasingly recognized as a mechanistic contributor to neurodegenerative disorders. Alzheimers disease (AD), characterized by amyloid pathology, synaptic dysfunction, and progressive neuronal loss, has recently been linked […]
- by Sun, H., Kahnert, K., Hansen, J. N., Leineweber, W. D., Li, M., Feng, W., Ballllosera Navarro, F., Axelsson, U., Ouyang, W., Lundberg, E.The spatial organization of proteins within cells governs virtually all cellular functions. Yet, current imaging technologies can simultaneously visualize only tens of proteins, orders of magnitude below the thousands that populate a single human cell. Here, we present ProtiCelli, a deep generative model that simulates microscopy images for 12,800 human proteins from just three cellular landmark stains. Trained on 1.23 million images from the Human Protein Atlas, ProtiCelli outperforms existing methods in reconstruction accuracy and textural fidelity, and generalizes to […]
- by Gouirand, N., Ibrahimi, M., Valotteau, C., Lecouffe, B., Le Bivic, A., Massey Harroche, D., Rico, F., Merkel, M., Delacour, D., Bazellieres, E.The development, maintenance and repair of epithelial tissues critically rely on adhesion complexes that ensure structural integrity while enabling dynamic remodeling. Such tissue remodeling underpins both physiological morphogenesis and pathological transformation. Central to these processes are mechanical forces, which tightly couple cytoskeletal organization to adhesion dynamics. Despite extensive investigations in two dimensional (2D) systems, how these interactions are orchestrated within polarized three dimensional (3D) epithelia remains largely unresolved. Here, we introduce a new, non invasive strategy to probe localized force […]
- by Chen, W., Maio, G., Chen, X., Lu, X., Zhao, J., Arora, N., Liu, Y., Ziolkowski, L. M., Macleod, K. F., Zhou, Y., Lin, H.KRAS mutations underlie many human cancers. While inhibitors such as Sotorasib and Adagrasib targeting KRAS mutants have shown promise, additional strategies are required to address the broader spectrum of KRAS-driven cancers, particularly those displaying drug resistance. Thus, there is a need to better understand KRAS signaling and develop new therapeutic strategies. Here we show that KRAS4A is palmitoylated on Cys180 by a palmitoyl transferase, DHHC7 (gene name ZDHHC7). Palmitoylation promotes KRAS4A plasma membrane localization, and more importantly, nanoclustering. This in […]
- by Milkey, A., Chen, J., Lewis, P. O.As modern phylogenomics datasets become increasingly large, it is useful to develop recommendations for how to subsample datasets for best species tree inference. Here we apply a new measure of phylogenetic information content that estimates the reduction in tree space occupied by a posterior sample of inferred trees relative to a prior sample in order to assess the effects of gene tree parameters on species tree estimation. We find that, consistent with earlier studies, when data are informative, more data […]
- by Fichtner, I. D., Temesvari-Nagy, L., Sahm, F., Gerstung, M., Bludau, I.Summary: ProteoPy is a lightweight Python library for protein- and peptide-level quantitative proteomics analysis, built around the AnnData class as its core data structure. It streamlines data import, preprocessing, and differential analysis while preserving all metadata within a single object. A reimplementation of our previously published COPF algorithm enables proteoform group inference directly from peptide-level data, facilitating the identification of proteoform-specific regulation and isoform usage. Designed for accessibility and flexibility, ProteoPy simplifies analysis for non-specialists and provides an extensible foundation […]
- by Xu, F.-Y., Wang, Y.-X.Despite the increased water content in fibrotic livers, numerous studies reported a decrease in ADC (apparent diffusion coefficient) in liver fibrosis. We argue that the ADC decrease in fibrotic livers is due to the T2 shine-through of ADC, as the longer T2 in liver fibrosis leads to less signal decay between the low and high b-value images. The metric slow diffusion coefficient (SDC) was proposed to mitigate the difficulties associated with this T2 shine-through of ADC. This study calculated ADC […]
- by Couturier, F., Cravero, C., Lesur, I., Confais, J., Belmonte, E., Piat, L., Marande, W., Rellstab, C., Valbuena, M., Saez-Laguna, E., Duvaux, L.We present a genome assembly from an individual specimen of Quercus canariensis (Fagaceae; Fagales; Magnoliopsida). The assembly was generated using PacBio HiFi long reads with an approximate sequencing depth of 39X and scaffolded using a reference-guided approach. The genome sequence has a total length of 816.0 megabases for haplotype 1 and 804.8 megabases for haplotype 2. The two haplotypes are each resolved into 12 chromosomal pseudomolecules, with only 3.48% and 1.36% of sequences remaining unplaced in haplotypes 1 and 2, […]
- by Bhattacharyya, D., Chatterjee, D., Panda, A. P., Ghosh, A. S.Despite multiple treatment strategies and extensive research on resistance mechanisms, tuberculosis (TB) remains a major global health threat, largely because of the rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. Among various mechanisms complicating the situation, active antibiotic export via efflux pumps is particularly significant, yet largely unexplored. Mycobacterium sp. encodes numerous transporters, many of which are overexpressed in clinical isolates or under drug stress. Here, we examined the possible role of Rv0783c, a putative transporter that is reportedly […]
- by Khan, H., Garcia-Galindo, P., Ahnert, S. E., Dingle, K.A morphospace is an abstract space of theoretically possible biological traits, shapes, or property values. It is interesting to explore which parts of a morphospace life occupies, as compared to those parts which could be occupied, but are not. Comparing random and natural non-coding (nc) RNA secondary structures is an established approach to studying morphospace occupation for RNA structures. Most earlier studies have focused on the minimum free energy (MFE) structure, while relatively few have looked at the Boltzmann distribution, […]
- by Chambers, O., Cadby, A. J.In contemporary bio-imaging-based research, computer-based assessment is becoming crucial for the characterisation of biological structures, as it minimises the need for time-consuming human annotation, which is prone to human error. Furthermore, it allows for the use of optical techniques that use lower photon intensities, thereby reducing reliance on high-intensity excitation and mitigating adverse effects on their activities. This study details the development and evaluation of sophisticated deep-learning models for amoeba detection using phase-contrast imaging. Using a single-class annotated dataset comprising […]
- by Carrillo Portillo, V. L., Taylor, P. W. J., Idnurm, A., Pearce, T. L., Scott, J., Vaghefi, N.Australia is the largest producer of Pyrethrum (Tanacetum cinerariifolium) globally. Amongst the constraints on production are the fungal pathogens Didymella tanaceti and Stagonosporopsis tanaceti, which pose a significant threat to the industry, causing substantial yield losses. While the infection biology of S. tanaceti is well characterised, knowledge of D. tanaceti and its potential interaction with S. tanaceti on plants remains limited, hindering disease management. We developed fluorescently labelled strains of both pathogens via Agrobacterium tumefaciens-mediated transformation (ATMT). Binary vectors carrying […]
- by Grier, A., Grenier, J. K., Byron, M. J., Fiani, N., Traver, N. D., Valm, A. M., Peralta, S.Background: Periodontitis (Perio) is a progressive oral disease characterized by inflammation and degradation of the periodontal apparatus and is associated with local and systemic morbidity including loss of teeth, cardiovascular disease, and diabetes mellitus, among others. Perio is highly prevalent in domestic canines and exhibits certain parallels in pathogenesis and pathophysiology to Perio in humans, although standard treatments are less effective. In both species, a complex interplay between oral microbiota and host immune response is implicated in the etiology of […]
- by Palma, L., Guzman, A. L., Marozzi, A., Del Valle, E. E., Castoldi, L.Agriculture has modified the soil structure due to the influence of external factors and processes that affect microbial biodiversity. Metagenomics is a fundamental tool for the study of soil microbial diversity because it provides information about the ecosystem diversity, including both the microorganisms that cannot be isolated in culture media and those that are no longer viable in the analyzed sample. In this work, six soil samples obtained from agroecosystems of central and northern Argentina were subjected to a preliminary […]